Congenital anomalies and health outcomes among survivors of childhood cancer: A report from the childhood cancer survivor study.
Bibliographic record
Abstract
e22021 Background: Although congenital anomalies are established risk factors for developing childhood cancer, less is known about health outcomes among survivors of childhood cancer with known congenital anomalies. Therefore, we estimated the risk of chronic health conditions (CHCs) and subsequent malignant neoplasms (SMNs) among survivors of childhood cancer by congenital anomaly status in the Childhood Cancer Survivor Study (CCSS). Methods: Overall, 22,247 five-year survivors self-reported congenital anomalies. We included 16 conditions present at birth, excluding self-reported genetic conditions. Patient-reported CHCs were graded using the Common Terminology Criteria for Adverse Events (CTCAE v. 4.03). Self-reported SMNs were confirmed through pathology report review. Hazard ratios (HR) of CHCs comparing survivors with vs. without congenital anomalies and their 95% confidence intervals (CI) were estimated using Cox regression with age as the time scale, adjusted for race/ethnicity, education, household income, health insurance, and original cancer treatment. Results: Among survivors (median age at cancer diagnosis 6 years (range 3-12), age at follow-up 31 years (range 25-39)), 16.9% (n = 3880) reported a congenital anomaly. The most common anomalies included: large/multiple birth marks (n = 1540, 40.4%); congenital heart defects (n = 693, 18.4%); and kidney, bladder, or genital abnormalities (n = 607, 14.6%). Relative to survivors without anomalies, those with anomalies more commonly had astrocytoma, Wilms tumor, and neuroblastoma primary cancers (p < 0.001), treated with radiation (p = 0.011), cyclophosphamide (p < 0.001), anthracyclines (p < 0.001), and epipodophyllotoxins (p = 0.044), and younger age at cancer diagnosis (11.3% vs. 5.7% diagnosed prior to one year of age, p < 0.001). Survivors with anomalies were more likely to develop any CHC (CTCAE grades 1-5 HR: 1.31, 95% CI: 1.23, 1.39); severe, disabling, life-threatening or fatal CHCs (grades 3-5 HR: 1.42 (95% CI: 1.28, 1.58); and multiple CHCs (≥2 conditions HR: 1.36, 95% CI: 1.27, 1.46; ≥3 conditions HR: 1.49, 95% CI: 1.37, 1.63). Survivors with anomalies had increased risk for adverse outcomes across multiple systems (all p < 0.001), including: hearing/vision/speech (HR: 1.37); urinary (HR: 1.42); hormonal/endocrine (HR: 1.24); heart/circulatory (HR: 1.35); digestive (HR: 1.49); and brain systems (HR: 1.42). We observed no differences in the risk of any SMN by congenital anomaly status (HR: 1.12, 95% CI: 0.90, 1.38). Conclusions: In our assessment, survivors of childhood cancer with self-reported congenital anomalies had an increased risk of developing CHCs compared to survivors without reported anomalies, but no increased risk of SMNs. Evaluating congenital anomalies allows identification of a population of childhood cancer survivors at high risk for poor long-term health outcomes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".